Identification of biomarkers that predict response to subthalamic nucleus deep brain stimulation in resistant obsessive–compulsive disorder: protocol for an open-label follow-up study

IntroductionDeep brain stimulation (DBS) of bilateral anteromedial subthalamic nucleus (amSTN) has been found to be helpful in a subset of patients with severe, chronic and treatment-refractory obsessive–compulsive disorder (OCD). Biomarkers may aid in patient selection and optimisation of this invasive treatment. In this trial, we intend to evaluate neurocognitive function related to STN and related biosignatures as potential biomarkers for STN DBS in OCD.Methods and analysisTwenty-four subjects with treatment-refractory OCD will undergo open-label STN DBS. Structural/functional imaging, electrophysiological recording and neurocognitive assessment would be performed at baseline. The subjects would undergo a structured clinical assessment for 12 months postsurgery. A group of 24 healthy volunteers and 24 subjects with treatment-refractory OCD who receive treatment as usual would be recruited for comparison of biomarkers and treatment response, respectively. Baseline biomarkers would be evaluated as predictors of clinical response. Neuroadaptive changes would be studied through a reassessment of neurocognitive functioning, imaging and electrophysiological activity post DBS.Ethics and disseminationThe protocol has been approved by the National Institute of Mental Health and Neurosciences Ethics Committee. The study findings will be disseminated through peer-reviewed scientific journals and scientific meetings.

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Tractography-Guided Deep Brain Stimulation of the Anteromedial Globus Pallidus Internus for Refractory Obsessive-Compulsive Disorder: Case Report

Neurosurgery ◽

10.1093/neuros/nyz285 ◽

2019 ◽

Cited By ~ 1

Author(s):

Amit Azriel ◽

Sarah Farrand ◽

Maria Di Biase ◽

Andrew Zalesky ◽

Elaine Lui ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Obsessive Compulsive Disorder ◽

Globus Pallidus ◽

Brain Stimulation ◽

Surgical Planning ◽

Globus Pallidus Internus ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Treatment Refractory ◽

Deep Brain

AbstractBACKGROUND AND IMPORTANCEObsessive-compulsive disorder (OCD) is a disabling psychiatric disorder, mainly treated with psychotherapy and pharmacotherapy. Surgical intervention may be appropriate for patients with treatment-refractory OCD. Deep brain stimulation (DBS) is an alternative for previously common ablative surgical procedures. Tractography has been proposed as a method for individualizing DBS treatment and may have the potential to improve efficacy.CLINICAL PRESENTATIONWe present a patient with treatment-refractory OCD previously treated with bilateral leucotomies, who underwent DBS surgery with targeting informed by tractography. Preoperative tractography to identify suitable DBS targets was undertaken. Structural images were also utilized for standard stereotactic surgical planning. The anteromedial globus pallidus internus (amGPi) was chosen as the target bilaterally after consideration of white matter projections to frontal cortical regions and neurosurgical approach. Bilateral amGPi DBS surgery was undertaken without adverse events. At 16-mo follow-up, there was a 48.5% reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale.CONCLUSIONThe amGPi can be a successful DBS target for OCD. This is the first known case to report on DBS surgery postleucotomies for OCD and highlights the utility of tractography for surgical planning in OCD.

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Deep Brain Stimulation of the Nucleus Accumbens for Treatment-Refractory Obsessive-Compulsive Disorder

Archives of General Psychiatry ◽

10.1001/archgenpsychiatry.2010.122 ◽

2010 ◽

Vol 67 (10) ◽

pp. 1061 ◽

Cited By ~ 404

Author(s):

Damiaan Denys ◽

Mariska Mantione ◽

Martijn Figee ◽

Pepijn van den Munckhof ◽

Frank Koerselman ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Nucleus Accumbens ◽

Obsessive Compulsive Disorder ◽

Brain Stimulation ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Treatment Refractory ◽

Deep Brain ◽

Stimulation Of

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Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-318996 ◽

2019 ◽

Vol 90 (7) ◽

pp. 805-812 ◽

Cited By ~ 16

Author(s):

Daniel Huys ◽

Sina Kohl ◽

Juan Carlos Baldermann ◽

Lars Timmermann ◽

Volker Sturm ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Nucleus Accumbens ◽

Executive Functions ◽

Obsessive Compulsive Disorder ◽

Brain Stimulation ◽

Internal Capsule ◽

Obsessive Compulsive ◽

Open Label ◽

Compulsive Disorder ◽

Deep Brain

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.

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Deep brain stimulation of the subthalamic nucleus in obsessive–compulsives disorders: long-term follow-up of an open, prospective, observational cohort

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323421 ◽

2020 ◽

Vol 91 (12) ◽

pp. 1349-1356

Author(s):

Stephan Chabardes ◽

Paul Krack ◽

Brigitte Piallat ◽

Thierry Bougerol ◽

Eric Seigneuret ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Safe Procedure ◽

Obsessive Compulsive ◽

Open Label ◽

Compulsive Disorder ◽

The Impact ◽

Deep Brain

BackgroundObsessive–compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD.MethodWe analysed, in a prospective, observational, monocentric, open label cohort, the effect of chronic non-motor STN-DBS in 19 patients with treatment-resistant OCD consecutively operated in a single centre. Severity of OCD was evaluated using the Yale and Brown Obsessive–Compulsive Scale (YBOCS). YBOCS scores at 6, 12 and 24 months postoperatively were compared with baseline. Responders were defined by >35% improvement of YBOCS scores. Global Assessment Functioning (GAF) scale was used to evaluate the impact of improvement.ResultsAt a 24-month follow-up, the mean YBOCS score improved by 53.4% from 33.3±3.5 to 15.8±9.1 (95% CI 11.2–20.4; p<0.0001). Fourteen out of 19 patients were considered as responders, 5 out of 19 being improved over 75% and 10 out of 19 over 50%. GAF scale improved by 92% from 34.1±3.9 to 66.4±18.8 (95% CI 56.7–76.1; p=0.0003). The most frequent adverse events consisted of transient DBS-induced hypomania and anxiety.ConclusionChronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management.

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Comparative effectiveness of neuroablation and deep brain stimulation for treatment-resistant obsessive-compulsive disorder: a meta-analytic study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319318 ◽

2019 ◽

Vol 90 (4) ◽

pp. 469-473 ◽

Cited By ~ 3

Author(s):

Kevin K Kumar ◽

Geoffrey Appelboom ◽

Layton Lamsam ◽

Arthur L Caplan ◽

Nolan R Williams ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Obsessive Compulsive Disorder ◽

Brain Stimulation ◽

Comparative Effectiveness ◽

English Language ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Treatment Refractory ◽

The Impact ◽

Deep Brain

BackgroundThe safety and efficacy of neuroablation (ABL) and deep brain stimulation (DBS) for treatment refractory obsessive-compulsive disorder (OCD) has not been examined. This study sought to generate a definitive comparative effectiveness model of these therapies.MethodsA EMBASE/PubMed search of English-language, peer-reviewed articles reporting ABL and DBS for OCD was performed in January 2018. Change in quality of life (QOL) was quantified based on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the impact of complications on QOL was assessed. Mean response of Y-BOCS was determined using random-effects, inverse-variance weighted meta-analysis of observational data.FindingsAcross 56 studies, totalling 681 cases (367 ABL; 314 DBS), ABL exhibited greater overall utility than DBS. Pooled ability to reduce Y-BOCS scores was 50.4% (±22.7%) for ABL and was 40.9% (±13.7%) for DBS. Meta-regression revealed no significant change in per cent improvement in Y-BOCS scores over the length of follow-up for either ABL or DBS. Adverse events occurred in 43.6% (±4.2%) of ABL cases and 64.6% (±4.1%) of DBS cases (p<0.001). Complications reduced ABL utility by 72.6% (±4.0%) and DBS utility by 71.7% (±4.3%). ABL utility (0.189±0.03) was superior to DBS (0.167±0.04) (p<0.001).InterpretationOverall, ABL utility was greater than DBS, with ABL showing a greater per cent improvement in Y-BOCS than DBS. These findings help guide success thresholds in future clinical trials for treatment refractory OCD.

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